Comparison of the end-of-life decisions of patients with hospital-acquired pneumonia after the enforcement of the life-sustaining treatment decision act in Korea.

BACKGROUND: Although the Life-Sustaining Treatment (LST) Decision Act was enforced in 2018 in Korea, data on whether it is well established in actual clinical settings are limited. Hospital-acquired pneumonia (HAP) is a common nosocomial infection with high mortality. However, there are limited data on the end-of-life (EOL) decision of patients with HAP. Therefore, we aimed to examine clinical characteristics and outcomes according to the EOL decision for patients with HAP. METHODS: This multicenter study enrolled patients with HAP at 16 referral hospitals retrospectively from January to December 2019. EOL decisions included do-not-resuscitate (DNR), withholding of LST, and withdrawal of LST. Descriptive and Kaplan-Meier curve analyses for survival were performed. RESULTS: Of 1,131 patients with HAP, 283 deceased patients with EOL decisions (105 cases of DNR, 108 cases of withholding of LST, and 70 cases of withdrawal of LST) were analyzed. The median age was 74 (IQR 63-81) years. The prevalence of solid malignant tumors was high (32.4% vs. 46.3% vs. 54.3%, P = 0.011), and the ICU admission rate was lower (42.9% vs. 35.2% vs. 24.3%, P = 0.042) in the withdrawal group. The prevalence of multidrug-resistant pathogens, impaired consciousness, and cough was significantly lower in the withdrawal group. Kaplan-Meier curve analysis revealed that 30-day and 60-day survival rates were higher in the withdrawal group than in the DNR and withholding groups (log-rank P = 0.021 and 0.018). The survival of the withdrawal group was markedly decreased after 40 days; thus, the withdrawal decision was made around this time. Among patients aged below 80 years, the rates of EOL decisions were not different (P = 0.430); however, mong patients aged over 80 years, the rate of withdrawal was significantly lower than that of DNR and withholding (P = 0.001). CONCLUSIONS: After the LST Decision Act was enforced in Korea, a DNR order was still common in EOL decisions. Baseline characteristics and outcomes were similar between the DNR and withholding groups; however, differences were observed in the withdrawal group. Withdrawal decisions seemed to be made at the late stage of dying. Therefore, advance care planning for patients with HAP is needed.

Impact of nutrition and physical activity on outcomes of hospital-acquired pneumonia.

Frailty is an important risk factor for adverse health-related outcomes. It is classified into several phenotypes according to nutritional state and physical activity. In this context, we investigated whether frailty phenotypes were related to clinical outcome of hospital-acquired pneumonia (HAP). During the study period, a total of 526 patients were screened for HAP and 480 of whom were analyzed. The patients were divided into four groups according to physical inactivity and malnutrition: nutritional frailty (Geriatric Nutritional Risk Index [GNRI] < 82 and Clinical Frailty Scale [CFS] ≥ 4), malnutrition (GNRI < 82 and CFS < 4), physical frailty (GNRI ≥ 82 and CFS ≥ 4), and normal (GNRI ≥ 82 and CFS < 4). Among the phenotypes, physical frailty without malnutrition was the most common (39.4%), followed by nutritional frailty (30.2%), normal (20.6%), and malnutrition (9.8%). There was a significant difference in hospital survival and home discharge among the four phenotypes (p = 0.009), and the nutritional frailty group had the poorest in-hospital survival and home discharge (64.8% and 34.6%, respectively). In conclusion, there were differences in clinical outcomes according to the four phenotypes of HAP. Assessment of frailty phenotypes during hospitalization may improve outcomes through adequate nutrition and rehabilitation treatment of patients with HAP.

Microbiologic pattern and clinical outcome of non-ICU-acquired pneumonia: Korean HAP registry analysis.

BACKGROUND/AIMS: Most studies on hospital-acquired pneumonia (HAP) have been conducted in intensive care unit (ICU) settings. This study aimed to investigate the microbiological and clinical characteristics of non-ICU-acquired pneumonia (NIAP) and to identify the factors affecting clinical outcomes in Korea. METHODS: This multicenter retrospective cohort study was conducted in patients admitted to 13 tertiary hospitals between July 1, 2019 and December 31, 2019. Patients diagnosed with NIAP were included in this study. To assess the prognostic factors of NIAP, the study population was classified into treatment success and failure groups. RESULTS: Of 526 patients with HAP, 379 were diagnosed with NIAP. Overall, the identified causative pathogen rate was 34.6% in the study population. Among the isolated organisms (n = 113), gram-negative bacilli were common pathogens (n = 91), such as Pseudomonas aeruginosa (n = 25), Acinetobacter baumannii (n = 23), and Klebsiella pneumoniae (n = 21). The multidrug resistance rates of A. baumannii, P. aeruginosa, and K. pneumoniae were 91.3%, 76.0%, and 57.1%, respectively. Treatment failure was significantly associated with K. pneumoniae (odds ratio [OR], 3.50; 95% confidence interval [CI], 1.35 to 9.05; p = 0.010), respiratory viruses (OR, 3.81; 95% CI, 1.34 to 10.82; p = 0.012), hematological malignancies (OR, 3.54; 95% CI, 1.57 to 8.00; p = 0.002), and adjunctive corticosteroid treatment (OR, 2.40; 95% CI, 1.27 to 4.52; p = 0.007). CONCLUSION: The causative pathogens of NIAP in Korea are predominantly gram-negative bacilli with a high rate of multidrug resistance. These were not different from the common pathogens of ICU-acquired pneumonia.

[Bronchopleural Fistula after Surgery: Therapeutic Efficacy of Bronchial Occluders]. / ìˆ˜ìˆ í›„ 기관지늑막루: Bronchial Occluder Device의 치료 효과.

Purpose: To evaluate the usefulness and effectiveness of bronchial occluders in the treatment of postoperative bronchopleural fistula (BPF). Materials and Methods: The subjects of the study were six out of seven postoperative BPF patients who underwent surgery due to tuberculosis or lung cancer between 2009 and 2019. Each patient had a bronchial occluder inserted to treat BPF that occurred after surgery. Of the six patients, five had lung cancers and one had tuberculosis. Five were male and one was female; their ages ranged from 59 to 74 years, with an average of 69 years. The diagnosis of BPF was based on findings from bronchoscopy and CT, and treatment was initiated approximately 1 to 2 weeks after diagnosis. The technical and clinical success of the bronchial occluders in the treatment of BPF was evaluated. The study assessed the postoperative clinical effects of the occluders, survival duration, and additional treatments. Results: All six patients were successfully treated. Clinical success was achieved in five patients, while partial clinical success was achieved in one; there was no clinical failure. No complications during the migration of the device or device perforations were observed. Two patients were diagnosed with BPF by CT, while four were diagnosed by bronchoscopy. Lobectomy, bilobectomy, and pneumonectomy were performed on two patients each. The periods between surgery and diagnosis ranged from 1 to 34 months; the average was 10 months. Four patients (59-103 days; an average of 80.5 days) died and two (313 days, 3331 days) survived. The causes of death were aggravation of the underlying disease (n = 2), pulmonary edema and pleural effusion (n = 1), and pneumonia (n = 1). Additional catheter drainage was performed in one patient, and a chest tube was maintained in two patients. Conclusion: Bronchial occluders are useful and effective in the treatment of BPF after pulmonary resection.

Safety and Efficacy of Pirfenidone in Advanced Idiopathic Pulmonary Fibrosis: A Nationwide Post-Marketing Surveillance Study in Korean Patients.

AIM: The efficacy and safety of pirfenidone have been previously demonstrated in patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF). However, the effect of pirfenidone in patients with advanced IPF remains unclear. Here, we investigated the effects of pirfenidone against advanced IPF in a real-world setting. METHODS: A prospective nationwide post-marketing study was conducted on 258 patients from 10 Korean institutions. Patients with a predicted forced vital capacity (FVC) less than 50% or a diffusing capacity of the lung for carbon monoxide (DLco) less than 35% at baseline were classified as the advanced IPF group. RESULTS: Of 219 patients included in the analysis, the majority were male (76.3%); the mean age was 67.3 years, and the advanced group accounted for 17.8% of the patients. The median treatment duration was 298 days. Among the subjects, 86.3% experienced adverse events (AEs), of which a decreased appetite (32.4%) and a photosensitivity reaction (13.7%) were the most frequent. The incidence of AEs was similar between the advanced and non-advanced groups (92.3% vs. 85.0%, respectively; p = 0.229). Although the overall discontinuation rate was higher in the advanced group than in the non-advanced group (74.4% vs. 50.0%, respectively; p = 0.006), the percentages of the patients who discontinued treatment as a result of AEs were similar in both groups (20.5% vs. 23.3%, respectively; p = 0.704). In all patients, the rates of decline in the predicted FVC and DLco over 48 weeks were - 4.3 ± 1.3% and - 4.4 ± 1.7%, respectively. There was no between-group difference in the rate of lung function decline. CONCLUSIONS: Pirfenidone used for the treatment of patients with IPF in a real-world setting was well tolerated, with an acceptable safety profile and a consistent therapeutic effect, regardless of the disease severity. TRIAL REGISTRATION: ClinicalTrials.gov NCT03761082; the trial was retrospectively registered on December 3, 2018.

Different histological types of triple metachronous primary lung carcinomas in 1 patient: Case report.

INTRODUCTION: The documented incidence of multiple primary lung cancer has increased as a result of the widespread use of early detection tools. We report the successful surgical treatment of a case who had consecutive metachronous adenocarcinoma and squamous cell carcinoma of the lung after successful treatment for small cell carcinoma of the lung.A 73-year-old man underwent a routine health check-up. Computed tomography showed ground-glass opacity in the upper lobe of the right lung, which was diagnosed as small cell carcinoma. Twenty-nine months after concurrent chemoradiotherapy for the carcinoma, which was in complete remission, a nodule was detected in the apical segment of the right upper lobe. Histopathologically, the tumor was diagnosed as poorly differentiated adenocarcinoma. The second metachronous adenocarcinoma was completely removed by right upper lobectomy with lymph node dissection. Seventeen months later, the patient underwent left upper lobectomy with lymph node dissection and received 4 cycles of adjuvant chemotherapy for another moderately differentiated squamous cell carcinoma. CONCLUSION: This case highlights the need for continuous screening for metachronous lung cancer following the successful treatment of primary lung cancer, even small cell carcinoma, to identify patients who could benefit from curative surgery.

Prevalence of Spirometrically-defined Restrictive Ventilatory Defect in Korea: The Fourth-2, 3, and Fifth Korean National Health and Nutrition Examination Survey, 2008-2012.

The aim of the study was to evaluate the prevalence of restrictive ventilatory defect and to determine the risk factors in subjects with spirometrically-defined restrictive ventilatory defect. We used the population-based, fourth-2, 3 (2008, 2009) and fifth (2010-2012) Korea National Health and Nutrition Examination Survey (KNHANES) to analyze 15,073 subjects, aged ≥40 yr who underwent spirometry. Chest radiographs were also analyzed to identify restrictive lung disease. Spirometrically-defined restrictive ventilatory defect (FEV1/FVC≥70% and FVC<80% of mean predicted value) was detected in 11.3% (n= 1,709) of subjects aged ≥40 yr. The prevalence increased to 12.3% on using the lower limit of normal (LLN) criteria. Approximately 99.4% of subjects were classified as mild restrictive. Among these, 11.3% had inactive tuberculosis (TB) lesion, 2.2% cardiac disease, 2.0% previous operation scar or radiation injury and/or mediastinal disease, and 7.4% other pulmonary disease suggestive of restrictive lung diseases on chest radiograph. Evidence of previous TB history was independently associated with restrictive ventilatory defect (odds ratios [OR], 1.78; 95% confidence interval, 1.45-2.18) after adjustment for gender, age, smoking, area for residence and body mass index. The prevalence of restrictive ventilatory defect among the nationwide population in Korea was 11.3% with fixed ratio criterion and 12.3% with LLN criterion. Most cases were of the mild restrictive category and previous TB history is the independent risk factor for restrictive ventilatory defect.

L-2-Oxothiazolidine-4-carboxylic acid or α-lipoic acid attenuates airway remodeling: involvement of nuclear factor-κB (NF-κB), nuclear factor erythroid 2p45-related factor-2 (Nrf2), and hypoxia-inducible factor (HIF).

Reactive oxygen species (ROS) play a crucial role in the pathogenesis of acute and chronic respiratory diseases. Antioxidants have been found to ameliorate airway inflammation and hyperresponsiveness in animal models employing short-term exposure to allergen. However, little data are available on the effect of antioxidants on airway remodeling and signaling pathways in chronic asthma. In the present study, we used a long-term exposure murine model of allergic airway disease to evaluate the effects of an antioxidant, L-2-oxothiazolidine-4-carboxylic acid (OTC) or α-lipoic acid (LA) on airway remodeling, focusing on the ROS-related hypoxia-inducible signaling. Long-term challenge of ovalbumin (OVA) increased ROS production, airway inflammation, and airway hyperresponsiveness, and developed features of airway remodeling such as excessive mucus secretion, subepithelial fibrosis, and thickening of the peribronchial smooth muscle layer. Administration of OTC or LA reduced these features of asthma, including airway remodeling, which was accompanied by suppression of transforming growth factor-ß1, vascular endothelial growth factor, and T-helper 2 cytokines. In addition, OVA-induced activation of nuclear factor-κB (NF-κB), nuclear factor erythroid 2p45-related factor-2 (Nrf2), hypoxia-inducible factor (HIF)-1α, and HIF-2α was reduced by OTC or LA. Our results also showed that OTC or LA down-regulated phosphoinositide 3-kinase activity and decreased phosphorylation of p38 mitogen-activated protein kinase but not extracellular signal-regulated kinase 1/2 or c-Jun N-terminal kinase. These findings demonstrate that OTC and LA can inhibit activation of NF-κB, Nrf2, and HIF, leading to attenuate allergen-induced airway remodeling.

PI3K-γ inhibition ameliorates acute lung injury through regulation of IκBα/NF-κB pathway and innate immune responses.

BACKGROUND: Acute lung injury (ALI) is a devastating disorder of the lung by various causes and its cardinal features are tissue inflammation, pulmonary edema, low lung compliance, and widespread capillary leakage. Among phosphoinositide 3-kinases (PI3Ks), PI3K-γ isoform has been shown to play an important role in a number of immune/inflammatory responses. METHODS: We investigated the role of PI3K-γ and its molecular basis in lipopolysaccharide (LPS)-induced ALI using a selective inhibitor for PI3K-γ, AS 605240, and LPS-treated C57BL/6 mice. RESULTS: Treatment of mice with LPS showed an increase of lung inflammation and vascular leakage. Production of reactive oxygen species (ROS), interleukin (IL)-1ß, tumor necrosis factor-α, and IL-4, adhesion molecule, and vascular endothelial growth factor (VEGF) was also increased. Administration of AS 605240 to LPS-treated mice markedly reduced the pathophysiological features of ALI and the increased production of ROS, cytokines, adhesion molecule, and VEGF in the lung. Our results also showed that treatment of mice with LPS activates nuclear factor-κB (NF-κB) and degradation of inhibitory κBα (IκBα) through PI3K-γ. Additionally, infiltration of dendritic cells (DCs) and expression of toll-like receptor 4 (TLR4) were significantly increased in the lung of LPS-treated mice, and inhibition of PI3K-γ reduced the infiltration of DCs and TLR4 expression in the lung. CONCLUSIONS: These results indicate that PI3K-γ is critically involved in LPS-induced ALI by regulating IκBα/NF-κB pathway and innate immune responses. Based on our data, we suggest that PI3K-γ isoform is a promising target for the treatment of ALI.

Bilateral multiple inflammatory myofibroblastic tumors of the lung successfully treated with corticosteroids.

Inflammatory myofibroblastic tumor (IMT) is a rare tumorous lesion that presents as a solitary nodule. Complete surgical resection is the standard treatment. However, due to its rarity, the optimal therapeutic strategy for multiple IMTs has not been defined. A 32-year-old man was referred to our hospital for evaluation of multiple pulmonary nodules. On computed tomography (CT) scan of the chest, there were a 3.0 × 1.7 cm mass with heterogeneous enhancement in the left upper lobe and multiple small nodules bilaterally. We performed wedge resection of the mass, and histopathology revealed IMT. He was treated with oral corticosteroids. The clinical and radiologic responses were so excellent that a CT scan showed complete resolution 1 month after the initiation of corticosteroid therapy. These observations suggest that corticosteroids may be the way to treat bilateral multiple IMT of the lung.

Pulmonary crystal-storing histiocytoma in a patient without a lymphoproliferative disorder.

Pulmonary crystal-storing histiocytoma is a very rare disorder and is characterized by infiltration of histiocytes with intracytoplasmic accumulation of crystallized immunoglobulins. It is usually associated with lymphoproliferative diseases or plasma cell dyscrasia. Here, we report a case of pulmonary crystal-storing histiocytoma in a 64-year-old man, presenting as a chronic pulmonary consolidation in the lung exposed to asbestos. Video-assisted thoracoscopic surgical biopsy displayed sheets of large, epithelioid histiocytes filled with a large number of needle-like crystals, showing the accumulation of crystallized polyclonal immunoglobulins. This lesion was consistent with crystal-storing histiocytosis or crystal-storing histiocytoma. With extensive clinical work-up, the current case was not associated with lymphoproliferative diseases. Herein, we present this extremely rare entity of pulmonary pathology, a pulmonary crystal-storing histiocytoma arising in the lung exposed to asbestos, and demonstrate the clinical, radiologic, and pathologic features of the tumor.

Pulmonary benign metastasizing leiomyoma in a postmenopausal woman.

Pulmonary benign metastasizing leiomyoma (BML) is a rare disease occurring predominantly in women of reproductive age and usually develops several years after the resection of a uterine leiomyoma. A 52-year-old postmenopausal woman was admitted to our hospital because of a right-sided empyema. Contrast-enhanced computed tomography showed a multiloculated pleural effusion on the right side and multiple small nodules in the left lung. A wedge biopsy revealed the pulmonary nodule consisting of branching glandular structures surrounded by abundant smooth muscle cells with no atypia. We performed a gynecologic examination to identify the primary origin of the pulmonary smooth muscle tumors. A uterine leiomyoma was found, and the patient underwent a total hysterectomy. Both pulmonary nodules and uterine leiomyoma were positive for estrogen and progesterone receptors. Therefore, we diagnosed the pulmonary lesions as BMLs. This is an interesting case of pulmonary BML identified simultaneously with uterine myoma in a postmenopausal woman. BML should be considered in women with multiple pulmonary nodules, even though it is rare.

Extra-axial chordoma presenting as a lung mass.

Chordomas are slow-growing, malignant tumors of bone that are thought to be derived from the primitive notochord and occur almost exclusively in the axial skeleton. The so-called extra-axial chordoma has been shown to demonstrate identical features to the classic chordoma, except that it is found outside the axial skeleton. Only six cases of extra-axial chordoma have been reported in the literature to date. In this report, we present another case of extra-axial chordoma for the first time originating from the lung parenchyma. A 79-year-old man presented a 7.3-cm-sized cavitary lung mass. Pathologic examination, including immunohistochemical studies, revealed that the mass was a chordoma. We report an extra-axial chordoma for the first time presenting as a lung mass.